DHEA Wins the Battle of the Bulge

Natural hormone reduces abdominal fat and improves insulin sensitivity in the elderly

People are not rats. Oh, sure, some people may deserve to be called rats, but they’re still human beings, more or less. That means, among other things, that they have appreciable amounts of a vital hormone called DHEA (dehydroepiandrosterone) in their systems. Rats, on the other hand, do not—nor do any other animals except primates. Is that important? You bet it is, if we’re trying to guess, from DHEA experiments with rats (or mice, etc.), what effects this compound might have in humans if they took it as a supplement.

For example, if treating rats with DHEA made them lose weight (as it does), would supplemental amounts make us lose weight too? If so, would we lose weight to a similar extent as the rats? And would the loss be via the same biochemical mechanism or a different one? Would the effect be one of appetite suppression, e.g., or of increased thermogenesis (fat burning), or both? Those questions are not easy to answer, but, considering the staggering amounts of fat we want to get rid of (collectively that is), it’s surely worth trying.

DHEA Is Bisexual (But Male)

A tremendous amount of biomedical research whose ultimate objective is to help improve the human condition is performed initially on rats to see if we can improve the rat condition. (Many other critters, especially mice, are also used, of course.) Underlying most rat research is the assumption that they are sufficiently like us physiologically that whatever works for them will probably work for us too. Experience has shown that this is a good assumption—most of the time. When we know, however, that rats, despite their high degree of physiological similarity to humans, don’t have DHEA in their systems, that’s a red-flag warning to be extra skeptical regarding our assumptions.

DHEA belongs to one of the most biologically potent classes of compounds there is—steroid hormones—and it occupies a central position in the web of biosynthetic pathways that produce sex hormones in our bodies. It’s produced from the “mother hormone,” pregnenolone, and is a precursor to both the male and female sex hormones (androgens and estrogens, respectively). Despite this “bisexual” orientation, DHEA is itself classified as an androgen.

DHEA Levels Drop 80% as We Age

It has been known for many years that giving DHEA to laboratory rats and mice induces fat loss. This naturally led to speculation that it might do the same in humans—but where’s the evidence? Until recently, there was none, but that has changed, thanks to a paper published by researchers at the Washington University School of Medicine in St. Louis, Missouri.¹ Their study (a randomized, double-blind, placebo-controlled trial) was designed to test the hypothesis that DHEA supplementation causes a decrease in abdominal fat and an increase in insulin sensitivity in elderly men and women. (Actually, the same authors had demonstrated a DHEA-induced decrease in total body fat in a preliminary study a few years earlier.²)

The researchers called their use of DHEA “replacement therapy” rather than supplementation, because DHEA levels, which soar during puberty and peak in our early twenties, decline steadily thereafter, to about 20% of our youthful levels by the time we reach our seventies. This decline occurs similarly in both men and women; it’s due primarily, if not exclusively, to a decrease in output from the adrenal glands, not to a change in metabolism. It’s accompanied by many age-related changes—e.g., shrinking muscle mass and decreasing bone density (which can lead to osteoporosis)—for which it may be responsible to one degree or another.

Obesity and Insulin Resistance Go Hand in Hand

Another such change is a tendency to develop abdominal adiposity (also known as a midriff bulge or a “spare tire”) and insulin resistance. The latter is the opposite of insulin sensitivity—it’s a declining ability, by aging cells, to respond adequately to the action of insulin as it tries to facilitate the transport of glucose (blood sugar) into the cells. Glucose is the primary fuel (fatty acids are also important) for cellular respiration, the biochemical process that powers life. Insulin resistance, if left untreated, can lead to chronic, excessive blood sugar levels, an extremely harmful condition that is the hallmark of type 2 (adult-onset) diabetes. This terrible disease can, in turn, lead to major complications (e.g., damage to the heart, brain, eyes, and kidneys) and a shortened life.

Expressed as a percentage of the 
initial amount of abdominal visceral 
fat, the men lost 7%, and the women 
lost 10%. Both the men and the 
women lost about 6% of their 
abdominal subcutaneous fat.

It’s no coincidence that obesity and insulin resistance seem to go hand in hand. Obesity is, in fact, by far the main cause of type 2 diabetes—which means that this disease is relatively easy to prevent. If you stay slim, your chances of getting diabetes will be slim. It’s important to note that abdominal obesity—a preponderance of fat accumulation in the midriff—is the kind most strongly implicated in the risk for diabetes and other degenerative diseases, such as atherosclerosis and heart disease.

Other Fat Fighters There’s more than one way to lose weight, and the judicious use of nutritional supplements is one of them. Diet and exercise are essential if you want to lose weight and be healthy, but why not exploit all your options? In the weight-loss arena, DHEA is in good company. Let’s look at a few other supplements with proven potential for fighting the fat. (For a more detailed discussion, see “Lose Weight with 5-HTP and EGCG” in the April 2003 issue.) Several studies by researchers at the University of Rome have shown that 5-HTP (5-hydroxytryptophan), the amino acid precursor to the neurotransmitter serotonin, is an appetite suppressant in obese women. Taking very large doses of 5-HTP (usually 900 mg/day) and with no dietary restrictions, the women lost about 2 1/2 to 3 1/2 lb, compared with the placebo group, over a 6-week period. The 5-HTP caused them to lose even more weight (about 5 1/2 lb, again vs. placebo) when all of them were placed on a 1200-calorie/day diet for a different 6-week period. Farther north, university researchers in Switzerland studied the effects of the polyphenolic compound EGCG (epigallocatechin gallate), the most biologically active component of green tea, in healthy young men. For 5–6 weeks, the men were restricted to a standard weight-maintenance diet and took a green tea extract that provided 270 mg/day of EGCG. Here the weight-reduction mechanism was not appetite suppression but thermogenesis, the generation of heat by physiological processes, such as the burning of fat in our cells. Compared with placebo, the green tea extract increased the men’s thermogenic energy expenditure by about 35–43%. Thus, while the Italian women’s caloric intake was decreased by appetite suppression with 5-HTP, the Swiss men’s caloric output was increased by thermogenesis with EGCG. The effect was the same: weight loss. It’s possible that the green tea extract’s effect may have been due in part to its caffeine content (which is much lower than that of coffee), through a synergistic interaction between the caffeine and the EGCG. Caffeine is an alkaloid that acts as a thermogenic agent in its own right, but it also boosts the thermogenic properties of other such agents.

Insulin Resistance—A Ticket for Diabetes

That brings us back to the Missouri researchers and their interest in DHEA as a possible means of helping people lose abdominal fat and avoid diabetes. For their study, they recruited 29 men and 27 women, aged 65–78 (average 71), who were overweight but not obese—their average body mass index (BMI) was 28.* They had all maintained a stable weight for at least 1 year, and none of them exercised regularly. None smoked. For the duration of the study (6 months), they took 50 mg/day of DHEA or placebo, at bedtime. (This dosage had previously been found to be safe for both men and women.³) So as not to skew the results of the study, they were asked not to alter their diet or physical activity.

*To compute your BMI, divide your weight in pounds by the square of your height in inches, and multiply the result by 703. (In metric units, divide your weight in kilograms by the square of your height in meters.) The ideal BMI range is about 19–22, and 23–24 is good. If your BMI is in the 25–29 range, you’re considered overweight—a moderate threat to your health and longevity. If it’s 30 or more, you’re obese, and you could be at serious risk of life-threatening diseases.

Using MRI (magnetic resonance imaging), the researchers measured the volunteers’ abdominal fat—both visceral and subcutaneous—at the outset of the study and again after 6 months. They also measured hormone and lipid levels, and they administered oral glucose tolerance tests, which are a measure of insulin sensitivity (or resistance). This test was done by taking blood samples after an overnight fast and again 30, 60, 90, and 120 minutes after the volunteers ingested 75 g of glucose dissolved in water. From these data, a graph can be plotted showing the rise and subsequent fall of the subject’s blood glucose during that 2-hour period. A curve that rises quickly to a high level and declines slowly thereafter means that the subject’s blood glucose levels were too high, too long—the classic signature of insulin resistance and the number one warning sign of impending diabetes.

DHEA Induces Fat Loss and Improves Insulin Sensitivity

The results of the study were gratifying indeed. They showed, first of all, that the 50-mg/day treatment increased the plasma DHEA levels in both the men and the women about 5-fold, restoring them to youthful levels. Concurrently, the plasma levels of estradiol (an estrogen) increased significantly in both the men and the women. By contrast, the women—but not the men—experienced significant increases in their plasma levels of testosterone (which is prosexual in women as well as in men). This finding may explain why DHEA is known to stimulate the libido in elderly women (especially those over 70) but not in elderly men.⁴* (For more on this, see “DHEA Helps Restore Hormonal Balance” in the March 2004 issue.)

*Another benefit of DHEA replacement therapy for women is that the normal, age-related loss of bone mass may be halted: DHEA apparently “stops the clock” on bone loss, and thus on the risk for osteoporosis. (See “Stopping the Biological Clock in Postmenopausal Women,” December 2001.)

The effects just described were already well known. More significantly, the study provided hard evidence of what many had long suspected: DHEA does induce fat loss in humans. Over the 6-month period, the men and women in the current study lost similar amounts, in absolute terms, of abdominal visceral fat. Because men are heavier than women, however, the relative losses were different: expressed as a percentage of the initial amount of fat, the men lost 7%, and the women lost 10%. Both the men and the women lost about 6% of their abdominal subcutaneous fat.

In conjunction with the abdominal fat losses, the researchers observed significant increases in insulin sensitivity (i.e., decreases in insulin resistance), providing further evidence that losing fat goes hand in hand with improved blood sugar control. They concluded,

These findings provide evidence that DHEA replacement may partially reverse the aging-related accumulation of abdominal fat in elderly people with low serum levels of DHEAS. They also raise the possibility that long-term DHEA replacement therapy might reduce the accumulation of abdominal fat and protect against development of the metabolic/insulin resistance syndrome.

“. . . DHEA replacement may 
partially reverse the aging-related 
accumulation of abdominal fat 
in elderly people with 
low serum levels of DHEAS.”

(DHEAS refers to DHEA sulfate, the chemical form in which about 90% of our DHEA exists in the bloodstream, having been converted to that form by the liver. The two forms are biologically equivalent.)

DHEA Has More Tricks Up Its Sleeve

The Missouri researchers could not easily have foreseen that similar results would be observed in the two sexes in their study. As we saw earlier with regard to testosterone levels, DHEA sometimes produces markedly different results in men and women, depending on the bodily system or process in question. A dual nature is a characteristic feature of this bisexual hormone.

In any case, we can be grateful for DHEA’s ability to help us lose some weight and control our blood sugar—which, by the way, are only two of the physiological tricks it has up its sleeve. To learn more about this somewhat mysterious and paradoxical molecule, see “DHEA—The Most Versatile Hormone” (February 2001), “DHEA—The Hormone of Youth?” (December 2002), “DHEA Protects Against Heart Disease and Diabetes” (October 2003), and the two articles cited earlier.

References

1. Villareal DT, Holloszy JO. Effect of DHEA on abdominal fat and insulin action in elderly women and men. JAMA 2004;292:2243-8.
2. Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf) 2000;53:561-8.
3. Legrain S, Massien C, Lahlou N, Roger M, Debuire B, Diquet B, Chatellier G, Azizi M, Faucounau V, Porchet H, Forette F, Baulieu ÉÉ. Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects. J Clin Endocrinol Metab2000;85(9):3208-17.
4. Baulieu ÉÉ, Thomas G, Legrain S, Lahlou N, Roger M, Debuire B, Faucounau V, Girard L, Hervy MP, Latour F, Leaud MC, Mokrane A, Pitti- Ferrandi H, Trivalle C, de Lacharrière O, Nouveau S, Rakoto-Arison B, Souberbielle JC, Raison J, Le Bouc Y, Raynaud A, Girerd X, Forette F. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci 2000 Apr 11;97(8):4279-84.